The present invention relates to a process for recovering medicinal substances or active substances from preparations, their initial products or waste, especially in the form of flat-shaped starting material, containing adhesively equipped film and active substance-containing material.
The process is especially suited for active substances from unused or discarded devices for the transdermal application of active substances and/or their process waste, whereby the active substances contained in said devices are usually present in combination with polymer films and polymer sheets.
Devices for transdermal application can be subdivided into two categories:
a) systems releasing active substances to the skin or to the organism by passive diffusion, and
b) systems releasing active substances to the skin or to the organism under the action or by the aid of electric currents.
Systems based on passive diffusion are so-called transdermal therapeutic systems (TTS).
These can be further subdivided into so-called matrix systems and reservoir systems.
In matrix systems, the active substance is dissolved in polymer films or partially suspended in crystalline form or in the form of microcapsules. In the simplest case, such systems therefore consist of a backing layer which is impermeable to the active substance, an active substance-containing and preferably self-adhesive matrix, and a protective sheet to be removed prior to use.
Reservoir systems contain the active substance in a fluid reservoir. The active substance may be present in a completely or only partially dissolved form. In the simplest case, these systems consist of a backing layer impermeable to the substances contained in the reservoir and a membrane at least permeable to the active substance and preferably provided with an adhesive film for application of the system to the skin.
Systems which release the active substance to the skin or the organism under application of electric current can have various structures. They are particularly used for active substances whichxe2x80x94owing to their chemo-physical propertiesxe2x80x94cannot penetrate the skin in a sufficient amount by means of passive diffusion.
A portion of unspent active substance remains in every worn TTS. Such active substance-containing waste products represent a toxicological or ecological risk and must therefore be disposed of as hazardous waste at extremely high expense. On the other hand, these waste products contain expensive and valuable ingredients or active substances originating from medicinal preparations, the recovery of which appears economically sensible. One reason why the economic considerations to be taken into account hereby result in favor of recovering active substances is that the carrier material, which is then substantially free of active substance, is not regarded as hazardous waste and can therefore be disposed of at a low cost.
A number of recycling methods are known from the state of the art, in particular also for recycling waste products containing adhesive-coated sheet material.
DE-OS 42 21 681 describes a method for recycling polyethylene, polypropylene or polystyrene adhesives on label waste products.
DE-OS 40 37 562 describes a recycling of adhesive-coated plastic films by repeated kneading in a solvent, drainage in a screw conveyor, and repeated passage of the remaining material in the same procedure. This publication also teaches a process for recycling plastic sheets coated with adhesive and present in shredded form by separating the plastic material and the adhesive. In a first stage, the sheet shreds are placed in a solvent for the adhesive and agitated under mechanical action for a predetermined period of time in order to disperse the adhesive adhering to the sheet shreds in the solvent. Subsequently, the adhesive dispersed in the solvent is separated from the sheet shreds under mechanical action. In a second, similar stage, fresh solvent is supplied to the sheet shreds of the first stage and the solvent-adhesive dispersion of the second stage is fed to the first stage.
DE-OS 195 24 083 describes a method for recycling TTS in which active substance is dissolved in a solvent and recovered from this solvent. However, the disclosure only states that the methods on which the invention is based are known to the person skilled in the art. In addition, this document suggests that the person skilled in the art submit the TTS to a pretreatment in order to sort out carrier and/or protective sheets, packaging material, etc.
It is the object of the present invention to provide, on this basis, a process with which it is possible to reprocess waste products of medical preparations and in particular of devicesxe2x80x94unused or discarded after wearingxe2x80x94for the transdermal application of active substances, so-called TTS, in a cost-efficient manner in order to recover active substances contained therein.
The method of the present invention is environmentally beneficial, economically feasible and enables the isolation of valuable raw active substances. It also results in an environmentally neutral and thus easily disposable fraction of residue of solids or carrier materials which are substantially free of active substances.
The carrier materials or residue from the process can be further recycled and disposed of according to known methods.
The process according to the invention avoids expensive process steps such as e.g. processing the materials in a pretreatment through sorting and separation into pure-grade fractions, whereby foreign materials such as carrier and/or protective sheets are sorted out and the active substance-containing material is concentrated. In the present invention, the separation is achieved by means of a complete dissolution of the active substances. An expensive size reduction of the material e.g. in a shredder, which is problematic even after embrittlement due to the pressure-sensitive adhesive characteristics, is not necessary. Rather, the dissolution and thus the prerequisite for the extraction of the active substance takes place in a liquid.
First, either an acidic extraction liquor having a pH from 1 to less than 7 or a basic extraction liquor having a pH of greater than 7 to less than 13 is added to laminates having an active substance.
Dissolution of the active substance may be intensified through additional heat treatment and/or agitation of the extraction liquor. Dissolution of the active substance may also be intensified through excitation of ultrasound in the extraction liquor.
To recover the active substance from the solution, it is advantageously provided that the recovery is carried out by precipitation.
If the active substances are extracted by means of solvents or solvent mixtures, it is advisable to use water with an acidic pH or an acidified water/alcohol mixture in the case of basic active substances and to set a basic pH value for acidic active substances. Inorganic acids or bases are particularly suitable, and especially aqueous solutions of sulfuric acid or sodium hydroxide solution with a concentration of 1%, because these substances are not volatile. The use of substantially aqueous solutions has the additional advantage that substantially lipophilic auxiliary agents are coextracted to only a small extent.
After filtering off the sheets or films, the active substances are precipitated by means of a pH shift. The thus obtained solution is filtered and the medicinal substance is purified by means of salification and/or recrystallization. The precipitation of a basic active substance can be carried out through acidification of the active-substance containing solution to a pH value of less than 6 by adding an inorganic acid.
The process is effective and economically advantageous and it achieves the object stated above in an optimum manner.
In particular the following substances can be recovered by a selection of the processing parameters: active substances with hormonal action, estradiol, estradiol derivatives, gestagens, gestagen derivatives or their mixtures, morphine or morphine derivatives, buprenorphine, physostigmine, scopolamine and galanthamine. The recovered substances can then be reused, according to their pharmaceutical action, as analgesics as well as for the treatment of senile dementia, high blood pressure, arrhythmia, vascular diseases, addictions, hyperlipidaemia, psychological disturbances, to influence blood coagulation, eating disorders, or dysglycemia.